The Intellectual and Developmental Disabilities (IDD) Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) sponsors research and research training aimed at preventing and ameliorating intellectual and developmental disabilities. The program supports biomedical, bio-behavioral, behavioral, and translational research in etiology, pathophysiology, screening, prevention, treatment, and epidemiology of these disorders. Down syndrome (DS; trisomy 21) is one ofthe most common genetic causes of intellectual disability, affecting 1 in 700 babies in the U.S. each year (1, 2), or an estimated total of -250,000 Americans living with Down syndrome in 2008 (3). Caused by the presence of 3 copies of chromosome 21 in most individuals, this condition is characterized by multiple organ system involvement in addition to intellectual disability. The molecular and cellular bases of intellectual disability due to Down syndrome have been a topic of intensive study, and murine models of the disease exist. The Repository of Mouse Models for Cytogenetic Disorders (Mouse Repository) began in the 1970s to generate and distribute mouse models for cytogenetic disorders, with special emphasis on Down syndrome (DS; trisomy 21). The creation of mouse models relevant to DS began in the 1970s and continued with the demonstration of genetic synteny between a segment of mouse chromosome 16 (Mmu16) and human chromosome 21 (Hsa21 ), which led to the use of the trisomy 16 mouse (Ts16) as a model for studies relevant to DS. With the subsequent genetic dissection of both mouse and human genomes, other genes present on Hsa21 were localized to mouse chromosomes 17 and I 0 (Mmu17 and Mmu l 0) as well. Pattial trisomies for a number of syntenic chromosomal segments were generated in the 1980s, under contract to NICHD. One of these partial trisomies, designated Ts65Dn, proved to include approximately 150 genes located in what is considered the Down syndrome critical region of Hsa21. Subsequently, these mice were produced and distributed, under an NICHD contract, to investigators approved for receipt of them by NICHD. During the last 22 years, various investigators have generated other models relevant to DS. These include, but are not limited to, TslCje, Ts2Cje, TslRhr, MslRhr, Tel, and others. When these strains and stocks have been made available to the research community, the creation of a central repository has ensured their maintenance on appropriate genetic backgrounds and their distribution to investigators upon request in a timely manner and subsequent to approval by NICHD. Many of these mouse strains are maintained under cryopreservation. In 2010, the NICHD reissued the contract A Repository of Mouse Models of Cytogenetic Disorders with a substantial increase in investment to ensure timely access to and increased availability of mouse models for cytogenetic disorders, particularly Ts65Dn, to the research community, and to ensure increased experimental efforts to modify the existing genetic backgrounds for the various strains to increase availability and ease of use by investigators. An RFI, NOT-HD-11-002 Request for Information (RFI): Acquisition, Processing, Storage and Distribution of Human Brain and Other Tissues to Advance Understanding and Treatment of Down Syndrome was released in 2011, and a substantial number of responses identified the need for increased availability of the mouse models to the research community as a priority issue. Subsequently, at a workshop Advancing Treatment for Alzheimer Disease in Individuals with Down Syndrome held in April, 2013, the Alzheimer disease and DS research and advocacy communities joined to advance the diagnosis and treatment of Alzheimer's disease in individuals with Down syndrome. One weakness identified by the participants in this meeting was the limited availability of existing model systems (other than the Ts65Dn mouse) to the research community at large. Since that meeting, the partial duplication strains Dup(16)Yey, Oup( l7)Yey, and Dup(lO)Yey have become available. Each of these strains contains a duplication of one of the 3 mouse chromosome regions that are syntenic to HSA21, with Dup(16)Yey representing the largest number of murine genes syntenic to the human chromosome 21.